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Journal of Orthopaedic Surgery and... May 2021Biochemical markers of bone turnover (BTMs), such as bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type...
BACKGROUND
Biochemical markers of bone turnover (BTMs), such as bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are commonly used for therapy monitoring purposes for osteoporotic patients. The present study evaluated the potential role of BTMs as therapy monitoring.
METHODS
All randomized clinical trials (RCTs) comparing two or more pharmacological treatments for postmenopausal osteoporosis were accessed. Only studies that reported the value of bALP, PINP, bCTx, and NTx at last follow-up were included. A multivariate analysis was performed to assess associations between these biomarkers and clinical outcomes and rate of adverse events in patients with postmenopausal osteoporosis. A multiple linear model regression analysis through the Pearson product-moment correlation coefficient was used.
RESULTS
A total of 16 RCTs (14,446 patients) were included. The median age was 67 years, and the median BMI 25.4 kg/m. The median vertebral BMD was 0.82, hip BMD 0.79, and femur BMD 0.64 g/cm. The ANOVA test found optimal within-group variance concerning mean age, body mass index, and BMD. Greater bALP was associated with lower femoral BMD (P = 0.01). Greater NTx was associated with a greater number of non-vertebral fractures (P = 0.02). Greater NTx was associated with greater rate of therapy discontinuation (P = 0.04). No other statistically significant associations were detected.
CONCLUSION
Our analysis supports the adoption of BTMs in therapy monitoring of osteoporotic patients.
LEVEL OF EVIDENCE
Level I, systematic review of RCTs.
Topics: Biomarkers; Bone Density; Bone Remodeling; Female; Humans; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic
PubMed: 34006294
DOI: 10.1186/s13018-021-02474-7 -
Medicine Apr 2021The aim of this study is to investigate the clinical efficacy of zoledronic acid (ZOL) in the treatment and prevention of osteoporotic vertebral compression fractures... (Meta-Analysis)
Meta-Analysis
Clinical efficacy of zoledronic acid combined with percutaneous kyphoplasty in the prevention and treatment of osteoporotic vertebral compression fracture: A systematic review and meta-analysis.
OBJECTIVE:
The aim of this study is to investigate the clinical efficacy of zoledronic acid (ZOL) in the treatment and prevention of osteoporotic vertebral compression fractures (OVCF) after percutaneous kyphoplasty (PKP) for elderly patients.
METHODS:
The PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and Embase were investigated through June 2020. All randomized controlled trials (RCT) involving ZOL injections for OVCF were enrolled. Outcome indicators included the bone mineral density (BMD), Visual Analog Scale (VAS), recompression vertebral fracture (RVF), Oswestry Disability Index (ODI), and bone metabolism (Procollagen type I N-terminal propeptide [PINP] and βcross-linked C-telopeptide of type I collagen [β-CTX]), bone cement leakage. Review Manager 5.3 was used to analyze these indicators.
RESULTS:
In this study, (1).. Eight studies had met the eligibility criteria, a total of 578 participants were involved (285 and 293 in the experimental (ZOL) group and control [no ZOL] group, respectively). (2).. The BMD scores of patients with OVCF in the experimental group were significantly higher than that in the control group ( < .05). The VAS scores were significantly different between the 2 groups at the 6, 12 months follow-up ( < .05). After PKP operation, ZOL injections reduced the rate of RVF ( < .05). In the comparison of ODI scores, the experimental group improved compared with the control group ( < .05). Respectively, the bone metabolism of patients with OVCF after ZOL was better than that of patients in control group ( < .05).
CONCLUSION:
Zoledronic acid had a significant effect on the treatment and prevention of OVCF in elderly osteoporotic patients after PKP. Due to the limited quality and data, more high-quality studies are needed to confirm the results of this meta-analysis.
Topics: Bone Density Conservation Agents; Humans; Kyphoplasty; Osteoporotic Fractures; Spinal Fractures; Zoledronic Acid
PubMed: 33787604
DOI: 10.1097/MD.0000000000025215 -
Medicine Jan 2021Osteoporosis (OP) results in an increased risk of fragility fractures, representing a major public health problem. In preventing OP, complementary and alternative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteoporosis (OP) results in an increased risk of fragility fractures, representing a major public health problem. In preventing OP, complementary and alternative medicine, such as acupuncture, was recommended because of the low efficiency and side effects of medications. Recently, there is insufficient evidence on electroacupuncture as an effective therapy for OP management. Hence, we evaluated the effectiveness of electroacupuncture for OP treatment.
METHODS
We conducted a systematic review and meta-analysis of clinical studies on patients with OP. Five databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang) were searched from the earliest publication date to March 12, 2020. Randomized controlled trials (RCTs) were included if electroacupuncture was applied as the sole treatment or as an adjunct to other treatments compared with medications in patients with OP. The measurement outcomes included serum aminoterminal propeptide of type I procollagen (PINP) and C-telopeptide of type I collagen (CTX) levels, bone mineral density (BMD) of lumbar, and visual analog scale scores for OP-related pain. Acupoints were extracted when available.
RESULTS
In total, 11 RCTs involving 731 participants were included for further meta-analysis. The meta-analysis showed that the use of electroacupuncture as a sole treatment or as an adjunct to other treatments could relieve OP-related pain compared with medications [mean difference (MD) = -0.58, 95% confidence interval (CI); MD = -0.97 to -0.19, P = .003, I2 = 88%; MD = -1.47, 95% CI = -2.14 to -0.79, P < .001, I2 = 96%). Meanwhile, the results showed a favorable effect of electroacupuncture on decreasing serum beta-CTX levels. However, there were no significant differences in serum PINP levels and BMD of lumbar. Shenshu (BL23) was the most frequent acupoint stimulation among these studies.
CONCLUSIONS
The application of electroacupuncture as an independent therapy or as an adjunct to other treatments might attenuate OP-related pain and serum beta-CTX levels. However, to overcome the methodological shortcomings of the existing evidence, due to a small size of samples and high risk of bias in these included RCTs, further rigorous studies are required.
Topics: Back Pain; Bone Density; Collagen Type I; Electroacupuncture; Humans; Osteoporosis; Peptide Fragments; Peptides; Procollagen
PubMed: 33546047
DOI: 10.1097/MD.0000000000024259 -
European Review For Medical and... Dec 2020The purpose of this study was to conduct a systematic review and meta-analysis analyzing the efficacy of zoledronic acid in improving outcomes with percutaneous... (Meta-Analysis)
Meta-Analysis
Efficacy of zoledronic acid with percutaneous kyphoplasty/vertebroplasty in the treatment of osteoporotic vertebral compression fractures: a systematic review and meta-analysis.
OBJECTIVE
The purpose of this study was to conduct a systematic review and meta-analysis analyzing the efficacy of zoledronic acid in improving outcomes with percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) surgeries for osteoporotic vertebral compression fracture (OVCF).
MATERIALS AND METHODS
We electronically searched the databases of PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar up to 15th September 2020. All types of studies assessing the use of zoledronic acid with PKP/PVP surgeries were included.
RESULTS
Seven studies were included. On meta-analysis of data from five studies reporting bone mineral density (BMD) as g/cm2, we found a statistically significant increase in BMD in the zoledronic group (MD: 0.14; 95% CI: 0.07, 0.21, I2=97%; p<0.001). On pooled analysis of two studies reporting T scores, a similar result in favour of the zoledronic acid group was noted (MD: 0.60; 95% CI: 0.23, 0.98, I2=76%; p=0.002). We also found a statistically significant reduction in pain scores (MD: -1.23; 95% CI: -1.59, -0.86, I2=97%; p<0.00001), ODI scores (MD: -9.54; 95% CI: -12.76, -6.31, I2=95%; p<0.00001) and serum type I procollagen peptide (CTX) levels (MD: -0.19; 95% CI: -0.25, -0.12, I2=98%; p<0.00001) with zoledronic acid as compared to control. Our analysis also found a significantly reduced risk of further vertebral fractures in patients receiving zoledronic acid as compared to control (RR: 0.17; 95% CI: 0.07, 0.39, I2=0%; p<0.00001).
CONCLUSIONS
Our review indicates that the use of once-yearly zoledronic acid in the peri-operative period of PVP/PKP procedures for patients with OVCF leads to significant improvement of BMD, reduced pain scores, better ODI scores, and reduced incidence of further vertebral fractures. Our results have clinical significance as it encourages the use of zoledronic acid for such patients for better clinical outcomes.
Topics: Combined Modality Therapy; Humans; Osteoporotic Fractures; Treatment Outcome; Vertebroplasty; Zoledronic Acid
PubMed: 33336756
DOI: 10.26355/eurrev_202012_24030 -
Journal of Hepatology Aug 2020The enhanced liver fibrosis (ELF) test has been proposed for the non-invasive assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
The enhanced liver fibrosis (ELF) test has been proposed for the non-invasive assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review to estimate the accuracy of this test against biopsy.
METHODS
In this systematic review, we searched MEDLINE, Embase, Web of Science and the Cochrane Library for studies that included patients with NAFLD and that used both liver biopsy (as the reference standard) and the ELF test. Two authors independently screened the references, extracted the data and assessed the quality of included studies. Due to the variation in reported thresholds, we used a multiple thresholds random effects model for meta-analysis (diagmeta R-package).
RESULTS
The meta-analysis of 11 studies reporting advanced fibrosis and 5 studies reporting significant fibrosis showed that the ELF test had a sensitivity of >0.90 for excluding fibrosis at a threshold of 7.7. However, as a diagnostic test at high thresholds, the test only achieved specificity and positive predictive value >0.80 in very high prevalence settings (>50%). To achieve a specificity of 0.90 for advanced and significant fibrosis, thresholds of 10.18 (sensitivity: 0.57) and 9.86 (sensitivity: 0.55) were required, respectively.
CONCLUSION
The ELF test showed high sensitivity but limited specificity to exclude advanced and significant fibrosis at low cut-offs. The diagnostic performance of the test at higher thresholds was found to be more limited in low-prevalence settings. We conclude that clinicians should carefully consider the likely disease prevalence in their practice setting and adopt suitable test thresholds to achieve the desired performance.
LAY SUMMARY
The enhanced liver fibrosis test has been suggested as a non-invasive blood test to aid the diagnosis of severe liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Our study results showed that the test has a high negative predictive value, especially in populations with low disease prevalence (likely encountered in primary care); so, it can exclude advanced fibrosis in patients with NAFLD. However, when prevalence is low, the positive predictive value of the enhanced liver fibrosis test is low, suggesting that additional strategies may be needed to make a positive diagnosis in such settings.
Topics: Algorithms; Biomarkers; Biopsy; Disease Progression; Humans; Hyaluronic Acid; Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Peptide Fragments; Predictive Value of Tests; Procollagen; Reference Standards; Tissue Inhibitor of Metalloproteinase-1
PubMed: 32275982
DOI: 10.1016/j.jhep.2020.03.036 -
Journal of Clinical Medicine Jun 2019This study seeks to evaluate the long-term effects of pharmacologic therapy on the bone markers and bone mineral density of transgender patients and to provide a basis... (Review)
Review
This study seeks to evaluate the long-term effects of pharmacologic therapy on the bone markers and bone mineral density of transgender patients and to provide a basis for understanding its potential implications on therapies involving implant procedures. Following the referred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and well-defined PICOT (Problem/Patient/Population, Intervention, Comparison, Outcome, Time) questionnaires, a literature search was completed for articles in English language, with more than a 3 year follow-up reporting the long-term effects of the cross-sex pharmacotherapy on the bones of adult transgender patients. Transgender demographics, time under treatment, and treatment received were recorded. In addition, bone marker levels (calcium, phosphate, alkaline phosphatase, and osteocalcin), bone mineral density (BMD), and bone turnover markers (Serum Procollagen type I N-Terminal pro-peptide (PINP), and Serum Collagen type I crosslinked C-telopeptide (CTX)) before and after the treatment were also recorded. The considerable variability between studies did not allow a meta-analysis. All the studies were completed in European countries. Transwomen (921 men to female) were more frequent than transmen (719 female to male). Transwomen's treatments were based in antiandrogens, estrogens, new drugs, and sex reassignment surgery, meanwhile transmen's surgeries were based in the administration of several forms of testosterone and sex reassignment. Calcium, phosphate, alkaline phosphatase, and osteocalcin levels remained stable. PINP increased in transwomen and transmen meanwhile, CTX showed contradictory values in transwomen and transmen. Finally, reduced BMD was observed in transwomen patients receiving long-term cross-sex pharmacotherapy. Considering the limitations of this systematic review, it was concluded that long-term cross-sex pharmacotherapy for transwomen and transmen transgender patients does not alter the calcium, phosphate, alkaline phosphatase, and osteocalcin levels, and will slightly increase the bone formation in both transwomen and transmen patients. Furthermore, long-term pharmacotherapy reduces the BMD in transwomen patients.
PubMed: 31159456
DOI: 10.3390/jcm8060784 -
Journal of Bone and Mineral Research :... Apr 2018Few pooled analyses of antiresorptive (AR) treatment trials relate short-term changes in bone turnover markers (BTMs) to subsequent fracture reduction. Such information... (Meta-Analysis)
Meta-Analysis
Few pooled analyses of antiresorptive (AR) treatment trials relate short-term changes in bone turnover markers (BTMs) to subsequent fracture reduction. Such information would be useful to assess new ARs or novel dosing regimens. In the Foundation for the National Institutes of Health (FNIH) Bone Quality project, we analyzed individual-level data from 28,000 participants enrolled in 11 bisphosphonate (BP) and three selective estrogen receptor modulator (SERM) placebo-controlled fracture endpoint trials. Using BTM results for two bone formation markers (bone-specific alkaline phosphatase [bone ALP] and pro-collagen I N-propeptide [PINP]) and two bone resorption markers (N-terminal and C-terminal telopeptide of type I collagen) and incident fracture outcome data, we performed a meta-regression relating the mean net effect of treatment on change in bone turnover (active minus placebo % difference after 3 to 12 months) to the log of study-wide fracture risk reduction, and used linear regression to plot the best fitting line. Separate analyses were performed for incident morphometric vertebral, nonvertebral, and hip fractures over 1 to 4 years of follow-up. Change in bone ALP and PINP were available for over 16,000 and 10,000 participants, respectively. For vertebral fracture, the results showed a strong relationship between treatment-related bone ALP or PINP changes and vertebral fracture risk reduction (r = 0.82 [p < 0.001] and r = 0.75 [p = 0.011], respectively) Relationships were weaker and no longer statistically significant for nonvertebral (r = 0.33 [p = 0.053] and r = 0.53 [p = 0.065], respectively) and hip fracture (r = 0.17 [p = 0.24] and r = 0.43 [p = 0.11], respectively) outcomes. Analyses limited to BP trials gave similar results. For all fracture types, relationships were weaker and nonsignificant for bone resorption markers. We conclude that short-term AR treatment-related changes in bone ALP and PINP strongly predict vertebral fracture treatment efficacy, but not nonvertebral or hip fracture treatment efficacy. Change in bone formation markers might be useful to predict the anti-vertebral fracture efficacy of new AR compounds or novel dosing regiments with approved AR drugs. © 2017 American Society for Bone and Mineral Research.
Topics: Alkaline Phosphatase; Biomarkers; Bone Remodeling; Bone Resorption; Diphosphonates; Estrogen Receptor Modulators; Female; Fractures, Bone; Humans; Incidence; Male; Peptide Fragments; Procollagen; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 29318649
DOI: 10.1002/jbmr.3355 -
Open Heart 2017Cardiac resynchronisation therapy (CRT) is an effective therapy for selected patients with heart failure (HF); however, a significant non-response rate exists. We... (Review)
Review
Extracellular cardiac matrix biomarkers in patients with reduced ejection fraction heart failure as predictors of response to cardiac resynchronisation therapy: a systematic review.
OBJECTIVE
Cardiac resynchronisation therapy (CRT) is an effective therapy for selected patients with heart failure (HF); however, a significant non-response rate exists. We examined current evidence on extracellular cardiac matrix (ECM) biomarkers in predicting response following CRT.
METHODS
Complete literature review of PubMed, Ovid SP MEDLINE, Cochrane Library and TRIP, reference lists, international cardiology conferences and ongoing studies between December 1999 and December 2015 conducted according to prospectively registered study selection and analysis criteria (PROSPERO:CRD42016025864) was performed. All observational and randomised control trials (RCT) were included if they tested prespecified ECM biomarkers' ability to predict CRT response. Risk of bias assessment and data extraction determined pooling of included studies was not feasible due to heterogeneity of the selected studies.
RESULTS
A total of 217 studies were screened; six (five prospective cohort and one RCT substudy) were included in analysis with 415 participants in total. Study sizes varied (n=55-260), cohort characteristics contrasted (male: 67.8%-83.6%, ischaemic aetiology: 40.2%-70.3%) and CRT response definitions differed (three clinical/functional, three echocardiographic). Consistent observation in all ECM biomarker behaviour before and after CRT implantation was not observed between studies. Lower type I and type III collagen synthesis biomarkers (N-terminal propeptides of type I and III procollagens) expression demonstrated replicated ability to predict reverse left ventricular remodelling.
CONCLUSION
Collagen synthesis biomarkers offer the most potential as ECM biomarkers for predicting CRT response. Heterogeneity between these studies was large and limited the ability to pool and compare results numerically. Use of different response definitions was one of the biggest challenges.
PubMed: 28878953
DOI: 10.1136/openhrt-2017-000639 -
Journal of the American Heart... Oct 2015There has been an increasing interest in use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure with preserved ejection fraction (HFPEF).... (Meta-Analysis)
Meta-Analysis Review
Effect of Mineralocorticoid Receptor Antagonists on Cardiac Structure and Function in Patients With Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction: A Meta-Analysis and Systematic Review.
BACKGROUND
There has been an increasing interest in use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure with preserved ejection fraction (HFPEF). However, a comprehensive evaluation of MRA effects on left ventricular (LV) structure and function in these patients is lacking. In this meta-analysis, we evaluated the effects of MRAs on LV structure and function among patients with diastolic dysfunction or HFPEF.
METHODS & RESULTS
Randomized, controlled clinical trials evaluating the efficacy of MRAs in patients with diastolic dysfunction or HFPEF were included. The primary outcome was change in E/e', a specific measure of diastolic function. Secondary outcomes included changes in other measures of diastolic function, LV structure, surrogate markers for myocardial fibrosis (carboxy-terminal peptide of procollagen type I [PICP] and amino-terminal peptide of pro-collagen type-II [PIIINP]), blood pressure, and exercise tolerance. In the pooled analysis, MRA use was associated with significant reduction in E/e' (weighted mean difference [WMD] [95% confidence interval {CI}]: -1.68 [-2.03 to -1.33]; P<0.0001) and deceleration time (WMD [95% CI]: -12.0 ms [-23.3 to -0.7]; P=0.04) as compared with control, suggesting and improvement in diastolic function. Furthermore, blood pressure and levels of PIIINP and PICP were also significantly reduced with MRA therapy with no significant change in LV mass or dimensions.
CONCLUSION
MRA therapy in patients with asymptomatic diastolic dysfunction or HFPEF is associated with significant improvement in diastolic function and markers of cardiac fibrosis without a significant change in LV mass or dimensions.
Topics: Chi-Square Distribution; Diastole; Fibrosis; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Recovery of Function; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling
PubMed: 26459931
DOI: 10.1161/JAHA.115.002137 -
PloS One 2015Lifespan and the proportion of older people in the population are increasing, with far reaching consequences for the social, political and economic landscape. Unless... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lifespan and the proportion of older people in the population are increasing, with far reaching consequences for the social, political and economic landscape. Unless accompanied by an increase in health span, increases in age-related diseases will increase the burden on health care resources. Intervention studies to enhance healthy ageing need appropriate outcome measures, such as blood-borne biomarkers, which are easily obtainable, cost-effective, and widely accepted. To date there have been no systematic reviews of blood-borne biomarkers of mortality.
AIM
To conduct a systematic review to identify available blood-borne biomarkers of mortality that can be used to predict healthy ageing post-retirement.
METHODS
Four databases (Medline, Embase, Scopus, Web of Science) were searched. We included prospective cohort studies with a minimum of two years follow up and data available for participants with a mean age of 50 to 75 years at baseline.
RESULTS
From a total of 11,555 studies identified in initial searches, 23 fulfilled the inclusion criteria. Fifty-one blood borne biomarkers potentially predictive of mortality risk were identified. In total, 20 biomarkers were associated with mortality risk. Meta-analyses of mortality risk showed significant associations with C-reactive protein (Hazard ratios for all-cause mortality 1.42, p<0.001; Cancer-mortality 1.62, p<0.009; CVD-mortality 1.31, p = 0.033), N Terminal-pro brain natriuretic peptide (Hazard ratios for all-cause mortality 1.43, p<0.001; CHD-mortality 1.58, p<0.001; CVD-mortality 1.67, p<0.001) and white blood cell count (Hazard ratios for all-cause mortality 1.36, p = 0.001). There was also evidence that brain natriuretic peptide, cholesterol fractions, erythrocyte sedimentation rate, fibrinogen, granulocytes, homocysteine, intercellular adhesion molecule-1, neutrophils, osteoprotegerin, procollagen type III aminoterminal peptide, serum uric acid, soluble urokinase plasminogen activator receptor, tissue inhibitor of metalloproteinases 1 and tumour necrosis factor receptor II may predict mortality risk. There was equivocal evidence for the utility of 14 biomarkers and no association with mortality risk for CD40 ligand, cortisol, dehydroepiandrosterone, ferritin, haemoglobin, interleukin-12, monocyte chemoattractant protein 1, matrix metalloproteinase 9, myelopereoxidase, P-selectin, receptor activator of nuclear factor KappaB ligand, sex hormone binding globulin, testosterone, transferrin, and thyroid stimulating hormone and thyroxine.
CONCLUSIONS
Twenty biomarkers should be prioritised as potential predictors of mortality in future studies. More studies using standardised protocols and reporting methods, and which focus on mortality rather than risk of disease or health status as an outcome, are needed.
Topics: Aged; Biomarkers; Cardiovascular Diseases; Cohort Studies; Female; Humans; Longevity; MEDLINE; Male; Middle Aged; Neoplasms
PubMed: 26039142
DOI: 10.1371/journal.pone.0127550